Clinical, Genetic, and Disability Profile of Pediatric Distal Hereditary Motor Neuropathy

Objective To describe the clinical, genetic, and disability profile of pediatric distal hereditary motor neuropathy (dHMN) and to determine the utility of an outcome measure validated for children with Charcot-Marie-Tooth disease (CMT) in assessing disability in this cohort. Methods We reviewed the clinical, neurophysiologic, and disability data on individuals with dHMN, evaluated before the age of 20 years, at 2 tertiary neuromuscular clinics in Australia and Spain. Disability was assessed annually with the CMT Pediatric Scale (CMTPedS) in a subset of individuals. Results Twenty-two children (13 female) from 19 families were included. Fourteen individuals were symptomatic in the first year of life. Intellectual disability was present in 6 individuals; upper motor neuron signs were seen in 8. Pathogenic variants were found in 9 families, more frequently in BICD2 (BICD2-4, DYNC1H1-2, MFN2-2, GARS-1). A novel pathogenic variant in the GARS gene was detected and characterized phenotypically. Disability was moderate on the CMTPedS (mean [SD] 18.2 [6.3], n = 16), with balance and long jump being the most affected and sensation items and grip strength the least affected. Over 1 year, the CMTPedS total score deteriorated, on average 1.5 points (SD 3.7) or 9% (n = 12), with significant variability in the rate of progression within the cohort. Conclusions The genetic profile of pediatric dHMN is different from that identified in adult cohorts. This study has identified distinct functional limitations for the CMTPedS in children and adolescents with dHMN.

Automated summary

This study describes the clinical and genetic profile of pediatric distal hereditary motor neuropathy (dHMN) and evaluates the utility of a validated outcome measure for children with Charcot-Marie-Tooth disease (CMT) in assessing disability in this cohort. The study found that the CMTPedS scale has distinct functional limitations when used in children and adolescents with dHMN, highlighting the need for tailored assessment tools for this population.